Since April, 59 children in Cambodia have fallen ill with symptoms that include respiratory illnesses, fever, and convulsions, according to the health ministry. Of those patients, 52 have died. Most were younger than 3 years old. Laboratory work is ongoing and a conclusive diagnosis is not yet in. But tests at Institut Pasteur du Cambodge in Phnom Penh point to hand, foot, and mouth disease, a contagious and sometimes fatal illness, head virologist Philippe Buchy wrote ScienceInsider in an e-mail.

A significant clue came when Institut Pasteur virologists tested cerebrospinal, throat, and rectal swab samples from 24 patients. Last weekend, throat and/or rectal swab samples from 15 patients tested positive for Enterovirus 71, one of the pathogens that causes hand, foot, and mouth disease. (The disease is different from foot-and-mouth disease, which infects cattle, sheep, and pigs.) The institute's scientists earlier had ruled out SARS, Nipah virus, and H5N1 and other influenza viruses as possible causes. They found strains of Streptococcus in throat samples from a number of patients but eliminated it as the cause of death after finding the same strains in samples from children with other symptoms.

Neighboring Vietnam has been badly hit by hand, foot, and mouth disease, so "we were expecting an outbreak sooner or later," Buchy says. But samples from victims did not initially test positive for Enterovirus 71. It was only after contacting scientists at the Oxford University Clinical Research Unit in Ho Chi Minh City, Vietnam, that the Pasteur team learned that the primers and probes they had designed for the virus in 2009 were out of date. Sequences of more recent Enterovirus 71 strains from Vietnam revealed that the virus had undergone significant genetic drift, Buchy says.

If Enterovirus 71 is indeed the culprit, one puzzling aspect may be the high number of fatal cases in a country of only 15 million people. Vietnam, which has a population roughly six times as large, confirmed only 20 deaths from hand, foot, and mouth disease between January and April of this year. In China, meanwhile, the health ministry announced last week that 240 people died of hand, foot, and mouth disease between January and May 2012. (The death toll has been higher this year than in years past, a ministry official told China Daily.)

While health officials have no idea how many people might be infected with hand, foot, and mouth disease in Cambodia, Buchy speculates that the population is largely naive to the virus and that "we may have a huge proportion of the child population that is not totally immune." Institut Pasteur scientists are now testing additional samples from the 24 patients and waiting for cell culture results. They will then start sequencing the Cambodian strain, Buchy says. Eventually, he says, they hope to determine "for how long and at which level the virus has been circulating" in Cambodia.

*This item has been updated on 10 July. A significant clue to the discovery that hand, foot, and mouth disease is making Cambodian children sick came when Institut Pasteur du Cambodge virologists tested not just cerebrospinal fluid, but also throat and rectal samples.